AIM To study the chemical constituents from the methanol fraction of Premna fulva Craib leaves and their anti-inflammatory activities.METHODS The methanol fraction from P.fluva were isolated and purified by TLC,column chromatography,and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Twelve compounds were isolated and identified as vitexin(1),balanophonin(2),inotodisaccharide(3),4-allyl-2,6-dimethoxyphenol-β-D-glucopyranoside(4),dehydrovomifoliol(5),loliolide(6),(E)-4-((1S,3R,4R)-1-hydroxy-4,5,5-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl)but-1-en-3-o-ne(7),(E)-4-hydroxyphenylprop-7-ene 4-O-β-D-glucopyranoside(8),4-O-β-D-glucopyranosylbenzoic acid(9),vicenin(10),oleanicacid(11),sesamin(12),respectively.Compounds 1,2,5,7,10,and 12 showed good inhibitory activities against NO,and the IC50 values were(26.42±2.5)、(21.24±2.2)、(25.88±1.9)、(29.72±2.1)、(8.90±1.1)、(9.73±0.7)μmol/L,respectively.CONCLUSION Compounds 2,4-8 are isolated from Premna genus plants for the first time.Compounds 1,2,5,7,10,12 have anti-inflammatory activities.

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

In recent years, the corona virus disease 2019 (COVID-19) pandemic has had a huge impact on the global medical, political and economic fields. Since the beginning of the COVID-19 epidemic, our understanding of the impact of COVID-19 has grown exponentially. Recently, the COVID-19 epidemic has changed rapidly in China, and there has been controversy over how to carry out surgical operations for patients with lung neoplastic lesions. Some studies have shown that lung cancer patients undergoing surgery are more likely to experience respiratory failure and perioperative death after contracting COVID-19 than the general population, however, delays in cancer treatment are also associated with increased mortality among these patients. In particular, the novel coronavirus Omikron variant has a higher transmissibility and may escape the immunity obtained through the previous novel coronavirus infection and vaccination. In order to minimize the risk of novel coronavirus infection in surgical patients, it is necessary to develop new treatment guidelines, expert consensus and preventive measures. However, the current rapid change of the epidemic situation has led to insufficient time and evidence to develop guidelines and consensus. Therefore, thoracic surgeons need to evaluate specific patient populations at higher risk of severe complications before surgery and weigh the benefit of surgical treatment against the risk of novel coronavirus infection. We try to give some recommendations on lung surgery during the current domestic epidemic situation based on the guidelines and consensus of oncology and thoracic surgery organizations in different regions on lung surgery.
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Humans ; Lung Neoplasms/complications* ; COVID-19 ; SARS-CoV-2 ; Multiple Pulmonary Nodules ; Pandemics/prevention & control* ; Lung

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

Objective Based on the techniques of continual tissue slices, the human epididymis was rebuilt for understanding the anatomical and histological features of the epididymal ducts. Methods Continuous tissue slices of one human epididymis were performed and digital slice images were obtained through scanning with Leica-Aperio AT2; the pipe wall of epididymal duct was aligned in sequence with Photoshop CC 2018 software and VGStudio MAX V3.0 software was used for three-dimensional synthesis. Finally, the later modification was carried out with Materialise Magics V22.0 software. Another human epididymis was used for electron microscopy. The histological features of epididymal ducts were analysed by combining slices and three-dimensional reconstruction. Results A total of 4331 and 543 slices in transverse and sagittal section respectively were prepared with a thickness of 7 |ira. According to the three-dimensional structure, regional distribution of human epididymal duct could be found obviously and the caput, corpus and cauda of epididymis could be clearly divided into 7, 9 and 4 subregions respectively. There were tissue intervals among adjacent subregions and epididymal ducts were disordered within each subregion, but differences were existed in tubular diameter and epithelial structure, and adjacent subregions were connected by single epididymal duct in the corpus and cauda. Conclusion The human epididymal duct can be successfully reconstructed by continual tissue slices technique. The human epididymal duct has regional distribution in space obviously and there are differences between different subregions.

MCT is an important key enzyme in the terpenoid biosynthesis in MEP pathway. In this study, Gateway technology was used to construct RNAi vector of TwMCT, and a vector fragment with a size of 484 bp was obtained. The TwMCT RNAi vector was transferred into the suspension cells of Tripterygium wilfordii by gene gun. Accumulation of terpenoids was assayed by UPLC, and the result showed that the content of triptolide and celastrol in cells decreased by 23.4% and 42.8%, respectively, compared with the control group pK7GWIWG2D. Moreover, the gene expression of TwMCT and major genes in terpenoid biosynthesis pathway was detected by qRT-PCR, which demonstrated that the expression of TwMCT reduced by 29.2% relative to that of the control group pK7GWIWG2D, and the relative expression of TwDXR, TwGGPS, TwHMGR and TwHMGS diminished by 36.3%, 31.3%, 62.2%, and 29.1%, respectively, but the expression of TwDXS was up-regulated by 114.2%, and there was no significant change in TwFPS. Thus, it was verified in vivo that interference with TwMCT expression significantly inhibited the accumulation of triptolide and celastrol in Tripterygium wilfordii, laying a foundation for further exploring the regulation mechanism of MCT gene on the terpenoid biosynthesis in Tripterygium wilfordii.

BACKGROUNDLaparoscopic liver resection (LLR) has been considered to be safe and feasible. However, few studies focused on the comparison between the anatomic and nonanatomic LLR. Therefore, the purpose of this study was to compare the perioperative factors and outcomes of the anatomic and nonanatomic LLR, especially the area of liver parenchymal transection and blood loss per unit area.

METHODSIn this study, surgical and oncological data of patients underwent pure LLR procedures for malignant liver tumor were prospectively collected. Blood loss per unit area of liver parenchymal transection was measured and considered as an important parameter. All procedures were conducted by a single surgeon.

RESULTSDuring nearly 5 years, 84 patients with malignant liver tumor received a pure LLR procedure were included. Among them, 34 patients received anatomic LLR and 50 received nonanatomic LLR, respectively. Patients of the two groups were similar in terms of demographic features and tumor characteristics, despite the tumor size was significantly larger in the anatomic LLR group than that in the nonanatomic LLR group (4.77 ± 2.57 vs. 2.87 ± 2.10 cm, P = 0.001). Patients who underwent anatomic resection had longer operation time (364.09 ± 131.22 vs. 252.00 ± 135.21 min, P < 0.001) but less blood loss per unit area (7.85 ± 7.17 vs. 14.17 ± 10.43 ml/cm 2 , P = 0.018). Nonanatomic LLR was associated with more blood loss when the area of parenchymal transection was equal to the anatomic LLR. No mortality occurred during the hospital stay and 30 days after the operation. Moreover, there was no difference in the incidence of postoperative complications. The disease-free and overall survival rates showed no significant differences between the anatomic LLR and nonanatomic LLR groups.

CONCLUSIONSBoth anatomic and nonanatomic pure LLR are safe and feasible. Measuring the area of parenchymal transection is a simple and effective method to estimate the outcomes of the liver resection surgery. Blood loss per unit area is an important parameter which is comparable between the anatomic LLR and nonanatomic LLR groups.

Aged ; Blood Loss, Surgical ; Female ; Humans ; Laparoscopy ; methods ; Length of Stay ; Liver ; pathology ; surgery ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Operative Time ; Postoperative Complications ; Prospective Studies